LTBP2 and congenital glaucoma

Autosomal recessive congenital glaucoma has been linked to biallelic loss‐of‐function variants in LTBP2. A homozygous LTBP2 mutation was identified in an individual presenting with congenital glaucoma and microspherophakia, with no family segregation data available (PMID:24908666). Early screening in a large Saudi cohort of CYP1B1‐negative newborn glaucoma cases failed to detect LTBP2 variants, underscoring genetic heterogeneity in this phenotype (PMID:21306220).

Functional studies demonstrate that Ltbp2(-/-) mice develop lens luxation secondary to deficient ciliary zonule microfibrils, whereas siRNA‐mediated LTBP2 knockdown in human ciliary epithelial cells disrupts microfibril meshwork formation. Addition of recombinant LTBP2 restores zonule integrity in both systems, supporting a loss‐of‐function mechanism in human congenital glaucoma (PMID:24908666).

Key Take-Home: Biallelic LTBP2 mutations cause autosomal recessive congenital glaucoma through disruption of ciliary zonule microfibril assembly, meriting inclusion of LTBP2 in genetic testing panels when common genes are negative.

References

• Human molecular genetics • 2014 • Latent TGF-β binding protein-2 is essential for the development of ciliary zonule microfibrils PMID:24908666
• Ophthalmic genetics • 2011 • Molecular characterization of newborn glaucoma including a distinct aniridic phenotype. PMID:21306220

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